Risk Of Nocturnal Hypoglycemia Research Articles

Optimal Use of Once-Weekly Basal Insulin Efsitora Alfa in Type 1 and Type 2 Diabetes: A Systematic Review and Meta-Analysis.

No meta-analysis has holistically analyzed and summarized the efficacy and safety of the novel once-weekly basal insulin efsitora alfa in managing type 1 diabetes (T1D) and type 2 diabetes (T2D). Clinical trials involving subjects with T1D and T2D receiving once-weekly efsitora alfa in the intervention arm and once-daily basal insulins in the control arm were searched throughout the electronic databases. The primary outcome assessed was the change from baseline in glycated hemoglobin (HbA1c). Data from 6 studies (2465 subjects) were analyzed (follow-up 26-54 weeks). Once-weekly efsitora alfa and once-daily degludec achieved comparable HbA1c reduction in study subjects with T2D (mean difference [MD] 0.02% [-0.11, 0.16]; P=.74) and T1D (MD 0.11% [-0.01, 0.22]; P=.08). Efsitora and degludec were similarly effective in reducing fasting plasma glucose and achieving HbA1c < 7% in subjects with T2D. Individuals with T2D and T1D in the 2 groups had comparable time in range, time above range, and time below range. Subjects with T2D receiving efsitora and once-daily basal insulin had comparable total adverse events, severe adverse events, injection-site reactions, hypersensitivity events, and overall and severe hypoglycemia; however, nocturnal hypoglycemia risk was lower with efsitora (risk ratio 0.85 [0.74, 0.98]; P=.03). However, in individuals with T1D, total adverse events, severe adverse events, and injection-site reactions were higher with efsitora, with comparable risks of hypersensitivity events and overall, severe and nocturnal hypoglycemia. Once-weekly basal insulin efsitora alfa is well tolerated with glycemic efficacy similar to once-daily degludec.

Continuous glucose monitoring in para cyclists: An observational study.

Continuous glucose monitoring (CGM) is an emerging tool for dietary counseling in athletes. This study aimed to explore blood glucose profiles in Para cyclists and evaluate CGM accuracy at rest and during exercise. Thirteen Para cyclists, comprising eight hand bikers and five cyclists, wore a CGM sensor (Abbott) for 2weeks. Participants recorded the timing of meals and regular training sessions and executed one standardized training session. Fifteen capillary blood glucose reference values (seven at rest and eight during the standardized training) were obtained by finger pricks. Mean glucose concentrations and time spent in hypoglycemia (<3.9mmol/L), euglycemia (3.9-7.8mmol/L), and hyperglycemia (>7.8mmol/L) were calculated over 24hrs and during daytime, nighttime, exercise, and 2hrs postprandial periods. Mean absolute relative differences (MARD) were calculated between the CGM and capillary blood glucose. The mean glucose concentration over the 24hr-period was 5.7 (5.6-5.8) mmol/L. Athletes were in the euglycemia range 91% of the time. Hyperglycemia was almost exclusively observed postprandially and during exercise. Hypoglycemia was restricted to the night and was particularly observed in athletes with a spinal cord injury. CGM accuracy was acceptable at rest (MARD: 12%) but markedly lower during exercise (MARD: 34%; p=0.01), especially for hand bikers (MARD: 41%) compared with cyclists (MARD: 24%; p=0.01). Para cyclists generally do not display signs of disturbed glucose regulation. However, the increased risk for nocturnal hypoglycemia in athletes with a spinal cord injury warrants attention. Furthermore, CGM accuracy is compromised during exercise, especially if the sensor is in proximity to highly active muscles.

Predicting risk for nocturnal hypoglycemia after physical activity in children with type 1 diabetes.

Children with type 1 diabetes (T1D) frequently have nocturnal hypoglycemia, daytime physical activity being the most important risk factor. The risk for late post-exercise hypoglycemia depends on various factors and is difficult to anticipate. The availability of continuous glucose monitoring (CGM) enabled the development of various machine learning approaches for nocturnal hypoglycemia prediction for different prediction horizons. Studies focusing on nocturnal hypoglycemia prediction in children are scarce, and none, to the best knowledge of the authors, investigate the effect of previous physical activity. The primary objective of this work was to assess the risk of hypoglycemia throughout the night (prediction horizon 9 h) associated with physical activity in children with T1D using data from a structured setting. Continuous glucose and physiological data from a sports day camp for children with T1D were input for logistic regression, random forest, and deep neural network models. Results were evaluated using the F2 score, adding more weight to misclassifications as false negatives. Data of 13 children (4 female, mean age 11.3 years) were analyzed. Nocturnal hypoglycemia occurred in 18 of a total included 66 nights. Random forest using only glucose data achieved a sensitivity of 71.1% and a specificity of 75.8% for nocturnal hypoglycemia prediction. Predicting the risk of nocturnal hypoglycemia for the upcoming night at bedtime is clinically highly relevant, as it allows appropriate actions to be taken-to lighten the burden for children with T1D and their families.

Development and Validation of a Nocturnal Hypoglycaemia Risk Model for Patients With Type 2 Diabetes Mellitus.

To develop and test different machine learning algorithms for predicting nocturnal hypoglycaemia in patients with type 2 diabetes mellitus. A retrospective study. We collected data from dynamic blood glucose monitoring of patients with T2DM admitted to the Department of Endocrinology and Metabolism at a hospital in Shanghai, China, from November 2020 to January 2022. Patients undergone the continuous glucose monitoring (CGM) for ≥ 24 h were included in this study. Logistic regression, random forest and light gradient boosting machine algorithms were employed, and the models were validated and compared using AUC, accuracy, specificity, recall rate, precision, F1 score and the Kolmogorov-Smirnov test. A total of 4015 continuous glucose-monitoring data points from 440 patients were included, and 28 variables were selected to build the risk prediction model. The 440 patients had an average age of 62.7 years. Approximately 48.2% of the patients were female and 51.8% were male. Nocturnal hypoglycaemia appeared in 573 (14.30%) of 4015 continuous glucose monitoring data. The light gradient boosting machine model demonstrated the highest predictive performances: AUC (0.869), specificity (0.802), accuracy (0.801), precision (0.409), recall rate (0.797), F1 score (0.255) and Kolmogorov (0.603). The selected predictive factors included time below the target glucose range, duration of diabetes, insulin use before bed and dynamic blood glucose monitoring parameters from the previous day. No Patient or Public Contribution.

What Really Matters?: How Insulin Dose, Timing, and Distribution Relate to Meal Composition in Free-Living People with Type 1 Diabetes.

Optimizing postprandial glucose control in persons with type 1 diabetes (T1D) is challenging. We hypothesized that in free-living individuals, meal composition (high and low glycemic index [HGI and LGI], high and low fat [HF and LF]) may impact insulin requirements. Adults (N = 25) with T1D using open-loop insulin and continuous glucose monitoring were provided a meal-tagging app and prepackaged meals with defined macronutrient content. Data from 463 meals were analyzed. LGI meals required significantly more insulin than HGI meals (P = 0.01). Furthermore, the mean (±standard deviation) carbohydrate-to-insulin ratio (CIR) was significantly different overall among the LGI-LF (5.5 ± 3.4), LGI-HF (4.5 ± 3.8), HGI-LF (7.6 ± 5.1), and HGI-HF (8.7 ± 5.8) meals (P = 0.001). The risk of nocturnal hypoglycemia is associated with daytime hypoglycemia and amount of insulin administered prior to the evening and exercise. This exploratory study designed to examine the impact of different meal types on insulin dosing requirements in free-living adults with T1D emphasizes the need for individualized adjustment of the CIR depending on meal composition.

239-OR: CGM Has a Specific Effect on the Reduction of Nocturnal Hypoglycemia in People with Type 1 Diabetes on an MDI Treatment Regimen

MDI users with type 1 diabetes may be less able to respond to circadian changes in insulin demand than CSII or AID users, which may increase the risk of nocturnal hypoglycemia. Therefore, we re-analyzed data from the HYPO.DE RCT to evaluate the effect of CGM on the percentage of low glucose levels &amp;lt; 70 mg/dl (% &amp;lt; 70 mg/dl) and &amp;lt; 54 mg/dl (% &amp;lt; 54 mg/dl) during 12 two-hour periods throughout the day. We compared 4-week baseline data from 141 participants using spot glucose monitoring (SMBG) with 4-week outcome data after a 6-month follow-up period in which the control group (n=66) remained on SMBG and the intervention group (n=75) used CGM (Dexcom G5). At baseline without CGM, there were significantly higher proportions of %&amp;lt;70 mg/dl or %54 mg/dl during the night (00:00 am - 06:00 am) than during the day (8.5 ±1.0% vs. 6.5 ±0.6%, p&amp;lt;0.001 respectively 4.0 ±0.6% vs. 2.4 ±0.3%, p&amp;lt;0.001). CGM had a greater effect on nocturnal hypoglycemia than on daytime hypoglycemia (see Figure 1). The greatest reduction in favor of the CGM users was between 04:00 a.m. and 06:00 a.m., with a between-group difference of -8.5% (95% CI -10.4% to -6.7%, p&amp;lt;.001) for %&amp;lt;70 mg/dl and -5.5% (95% CI 4.4 - 6.6%, p&amp;lt;.001) for %&amp;lt;54 mg/dl. The data suggest that CGM provides benefits to MDI users with type 1 diabetes in preventing nocturnal hypoglycemia, potentially compensating for lack of responsiveness to a circadian changing insulin demand. Disclosure N. Hermanns: Speaker's Bureau; Berlin-Chemie AG, Sanofi-Aventis Deutschland GmbH. Research Support; Sanofi-Aventis Deutschland GmbH. Speaker's Bureau; Roche Diabetes Care. Research Support; Roche Diabetes Care. Speaker's Bureau; Dexcom, Inc. Advisory Panel; Abbott Diagnostics, Ypsomed AG. D. Ehrmann: Advisory Panel; Dexcom, Inc. Speaker's Bureau; Dexcom, Inc., Sanofi-Aventis Deutschland GmbH. Advisory Panel; Roche Diabetes Care. Speaker's Bureau; Roche Diabetes Care, Berlin-Chemie AG. B. Kulzer: Advisory Panel; Abbott Diagnostics, Berlin-Chemie AG, Dexcom, Inc., Sanofi, embecta, Novo Nordisk, Roche Diabetes Care. Speaker's Bureau; Bayer Inc., Insulet Corporation, Lilly Diabetes. G. Freckmann: Advisory Panel; Abbott. Research Support; Ascensia Diabetes Care. Advisory Panel; Boydsense, Dexcom, Inc., Lilly Diabetes. Speaker's Bureau; Novo Nordisk. Advisory Panel; Perfood, PharmaSens. Consultant; Roche Diabetes Care. Research Support; Roche Diabetes Care. Consultant; Sinocare. Speaker's Bureau; Terumo Corporation. Consultant; Ypsomed AG. L. Heinemann: Stock/Shareholder; Science Consulting in Diabetes GmbH, Profil Institut für Stoffwechselforschung GmbH. Advisory Panel; embecta. Board Member; Lifecare A/S. Stock/Shareholder; diateam GmbH. Funding The HYPO.DE study was funded by Dexcom, San Diego

FRI654 Concentrated Regular U-500 Insulin In An Automated Insulin Delivery System: A Case Report

Abstract Disclosure: J. Aurora: None. A. Saraswat: None. Background: Concentrated regular U-500 (U-500R) insulin is commonly used in patients with T2DM who are highly insulin-resistant, requiring more than 200 units of insulin per day. Utilizing U-500R reduces the number of daily injections, decreases injection volume, and improves cost effectiveness. There have been clinical trials using U-500R for continuous subcutaneous insulin infusion (CSII), particularly in Omnipod which has been shown to improve glycemic control and patient satisfaction without an increase in hypoglycemia (1). In addition, U-500R administration via multiple daily injections (MDI) and an investigational U-500R CSII, have been compared and demonstrated improved glycemic control with both modalities, but an increase in nocturnal hypoglycemia with CSII (2). Automated insulin delivery (AID) systems, or hybrid closed loop systems, have not formally been studied in patients with T2DM using U-500R. We present a case of a patient with T2DM with high insulin resistance using U-500R with Omnipod 5 AID system. Clinical Case: A 54-year-old female with T2DM with high insulin resistance was initially on Omnipod Dash with U-100 insulin lispro with baseline A1c 12.1%. She was transitioned to Omnipod 5 in 2022, and over 4 months A1c improved to 8.8%, GMI 8.8%, TIR 38%, TAR 62%, TBR 0%, CV 35.9%, and automated mode 97%. However, her total daily dose was 134 units leading to pod changes every 1.5 days. She expressed interest in switching to U-500R to reduce pod changes while utilizing her current CSII technology. We switched to U-500R, continued automated mode, increased her 24-hour BG target from 120 mg/dL to 130 mg/dL to reduce hypoglycemia risk, and increased her active insulin time from 3 to 6 hours to reflect U-500R kinetics. After 4 weeks, her GMI improved to 8.0%, TIR 47%, TAR 52%, TBR 1%, CV 45.9%, and automated mode 94%. Although nocturnal BG readings were normal, ranging from 70-130 mg/dL, she was having nightly symptoms of relative hypoglycemia. We then adjusted her BG target overnight to 150 mg/dL, which kept BG between 80-130 mg/dL with resolution of her symptoms. Conclusion: U-500R proved to be safe and effective with Omnipod 5 AID. Despite setting a higher BG target, the algorithm continuously kept BG well below this, particularly overnight. However, the safety mechanisms incorporated with the CSII suspended insulin delivery for predicted hypoglycemia. Further research will be required to adapt the automated dosing algorithm to U-500R to reduce the risk of nocturnal hypoglycemia.

575-P: Do Overnight Dips Exist following Afternoon Exercise? Factors Associated with Nocturnal Hypoglycemia in the Type 1 Diabetes Exercise Initiative Pediatric (T1DexiP) Study

Some controlled studies have associated afternoon exercise with a biphasic pattern of hypoglycemia (hypo) risk: during exercise and 7-11hrs later. We explored factors relating to nocturnal hypo following afternoon exercise (12PM-6PM) among youth in the observational T1DexiP study. Youth with T1D (n=203; [mean±SD] age14±2 yrs; HbA1c=7.0± 1.2%; 42% female; T1D duration 5.4±3.9yrs; 12% on MDI and 58% on AID) wore a continuous glucose monitor, an activity monitor and logged activity using the Bant app for 10 days. Repeated measures logistic regression adjusted for bedtime glucose and % time below range (TBR &amp;lt; 70mg/dL) in the prior 24hrs. Of the 833 afternoon exercise sessions, 14% led to nocturnal hypo (≥15 consecutive minutes &amp;lt;70 mg/dL). Median TBR was higher in the 24hrs before exercise in youth who developed nocturnal hypo vs those who did not (3% vs 1%), while pre-exercise glucose level, heart rate, and insulin on board were similar. Nocturnal hypo risk was higher among teens who exercised more often during the study (Table). A trend for lower risk was noted with AID use. Our model revealed that participants who exercised &amp;gt;90 min/day had increased risk of nocturnal hypoglycemia, while AID use may reduce risk. This suggests algorithmically modulated insulin delivery may help to mitigate the impact of afternoon exercise on nocturnal glycemia. Disclosure J.Sherr: Advisory Panel; Bigfoot Biomedical, Inc., Insulet Corporation, Medtronic, Vertex Pharmaceuticals Incorporated, Cecelia Health, StartUp Health T1D Moonshot, Consultant; Bigfoot Biomedical, Inc., Insulet Corporation, Medtronic, Lilly, Research Support; Insulet Corporation, Medtronic, NIH - National Institutes of Health, Juvenile Diabetes Research Foundation (JDRF), Speaker's Bureau; Insulet Corporation, Zealand Pharma A/S, Lilly, Medtronic. S.Bergford: None. S.R.Patton: None. M.A.Clements: Consultant; Glooko, Inc., Research Support; Dexcom, Inc., Abbott Diabetes. P.Calhoun: None. R.L.Gal: None. M.Riddell: Advisory Panel; Zealand Pharma A/S, Zucara Therapeutics, Indigo Diabetes, Consultant; Lilly Diabetes, Eli Lilly and Company, Jaeb Center for Health Research, Speaker's Bureau; Dexcom, Inc., Novo Nordisk, Sanofi, Stock/Shareholder; Supersapiens, Zucara Therapeutics. T1dexip study group: n/a. Funding The Leona M. and Harry B. Helmsley Charitable Trust; Dexcom, Inc.

Glucocorticoid-induced hyperglycemia and diabetes: Practical points

Glucocorticoids are widely used in medical practice for their anti-inflammatory action, but lead to hyperglycemia in 30% of cases, due to rapid reduction of insulin secretion and action. Endogenous glucose production is less strongly suppressed by insulin, even small doses such as 7.5mg/day. As they are administered in the morning, glucocorticoids induce hyperglycemic excursion in the afternoon, and at this time screening can be performed by capillary glucose measurement. It is also critical to determine, on medical history and HbA1c assay, whether the patient had prior diabetes, sometimes overlooked, in which case diabetes will not resolve after glucocorticoid discontinuation, and poorly controlled diabetes will often require a basal-bolus insulin therapy in the meantime. This heavy therapy is not suitable for de novo diabetes, as it incurs a risk of nocturnal hypoglycemia, whereas intermediate-acting morning insulin injection provides better cover of hyperglycemia in the afternoon. The British Diabetology Societies recently reported that an even simpler prescription of gliclazide in the morning may be sufficient for some patients. The antidiabetic treatment will have to be monitored, and reduced when glucocorticoid dose is scaled off. Other antidiabetic agents are being tested in trials to develop simple alternatives without risk of hypoglycemia.

Effects of Physical Activity Timing and Intensity on the Occurrence and Risk of Nocturnal Hypoglycemia in Adolescents With Type 1 Diabetes

Clinical Scenario: Athletic trainers should be aware of how physical activity may influence the risk of nocturnal hypoglycemia in adolescents with type 1 diabetes (T1D). Clinical Question: Does the timing and intensity of physical activity affect the occurrence and risk of nocturnal hypoglycemia in adolescents with T1D? Results of the Search: Four studies meeting the inclusion criteria were found and included in the appraisal. Three studies were prospective observational cohorts, and one was a randomized case-crossover study. Clinical Bottom Line: Adolescents with T1D may be at greater risk of nocturnal hypoglycemia after performing 30–60 minutes of moderate-to-vigorous physical activity during the late afternoon or evening. Implications: Athletic trainers should educate adolescents with T1D and their parents about the risk of nocturnal hypoglycemia after MVPA, and work in collaboration with the diabetes care physician to ensure prevention techniques are included in the patient'’s diabetes care plan. Level of Evidence: Strength of Recommendation Taxonomy Grade B.

The comparative analysis of efficacy and safety parameters of Insulin Degludec versus Insulin Glargine: A Narrative Review

Background and aim: Insulin degludec and insuline glargine are the two long-acting insulins most commonly prescribed for the treatment of Diabetes Type 1 as well as Diabetes Type 2. Both insulins were generated to address a clinical need for the basal insulin which produces a more even and flat activity profile and reduces the number of hypoglycemia- a dangerous side effect of insulin therapy. Although glargine and degludec confirmed their superiority in terms of reduced rate of hypoglycemia, especially in comparison with first generations, several studies revealed that degludec is associated with less glycemic variability. Moreover, degludec is more effective in reaching better fasting plasma glucose levels without increasing a risk of nocturnal hypoglycemia. The aim of this study is to compare the five most essential efficacy and safety parameters of insulin degludec versus insulin glargine. Methods: This study used a narrative synthesis of the research findings. The search for existing narrative and systematic reviews on the research topic was conducted through PubMed, Embase, and Google Scholar electronic databases. Reviews were selected according to a study design and methodological quality of the included studies. The reviews published within 2015-2023 period were included. The data on five safety and efficacy parameters (the reduction of fasting plasma glucose level, HbA1c levels, overall and nocturnal hypoglycemia episodes, body weight gain) were retrieved for the analysis. Findings: The analysis of data retrieved out of 10 systematic reviews confirmed superiority of insulin degludec in comparison with insulin glargine in terms of four safety and efficacy parameters. The treatment with degludec was associated with fewer overall and nocturnal hypoglycemia episodes, a better reduction of fasting plasma glucose levels in both Diabetes Type 1 and Diabetes Type 2 groups (insulin naïve and experienced) patients, less weight gain in Diabetes Type 2 insulin experienced group and Diabetes Type 1 groups. Both insulins provided a similar reduction of HbA1c levels among patients with Diabetes Type 1 and Diabetes Type 2. Conclusion: In conclusion, this narrative review revealed that insulin degludec is superior to insulin glargine in terms of four safety and efficacy parameters such as change in fasting plasma glucose, body weight gain, nocturnal and overall hypoglycemia episodes. Degludec and glargine produced similar changes in HbA1c levels. The most pronounced differences in almost all the examined reviews were detected in the variables indicating nocturnal and overall hypoglycemia. The treatment with degludec also resulted in less hypoglycemia, accompanied with a better reduction of fasting plasma glucose levels. This characteristic confirms that degludec produces less glycemic variability and a close to physiological activity profile.

EE507 Insulin Degludec/Insulin Aspart Versus Basal+Bolus Insulin Treatment (Insulin Glargine U100 & Insulin Aspart) in T2D in India: A Short-Term Cost-Effectiveness Analysis Based on the Step-By-Step Clinical Trial

The Step-by-step clinical trial (NCT02906917) in basal insulin ± oral antidiabetic drugs treated people with type 2 diabetes (T2D) confirmed a similar glycemic effect for insulin degludec/insulin aspart (IDegAsp) versus basal+bolus insulin treatment (BB) of IGlar U100 + IAsp that was consistent over 38-weeks period with a significantly lower risk of nocturnal hypoglycemia. The aim of the present analysis was to assess the short-term cost-effectiveness of IDegAsp vs BB in Indian setting.

Confirmation of the Absence of Somogyi Effect in Patients with Type 2 Diabetes by Retrospective Continuous Glucose Monitoring Systems.

Background The Somogyi effect is defined as fasting hyperglycemia secondary to nocturnal hypoglycemia. In past decades, this effect proved to be rare or absent. However, many endocrinologists still believe in this phenomenon in clinical practice. Does the Somogyi effect truly exist? We aimed to answer this question with a study based on a larger sample size. Methods We collected retrospective CGMs data from 2,600 patients with type 2 diabetes with stable treatment of insulin. Nocturnal hypoglycemia was defined as a CGMs sensor glucose of less than 3.9 mmol/L for at least 15 min between 24:00 and 06:00. Morning fasting glucose was compared between people with nocturnal hypoglycemia and without nocturnal hypoglycemia. Results Valid CGMs data were obtained on 4,705 of 5,200 nights. Morning fasting glucose was observed lower after nights with nocturnal hypoglycemia compared with nights without hypoglycemia (P < 0.001). 84 cases presented fasting glucose of more than 7 mmol/L after nocturnal glucose of less than 3.9 mmol/L. Only 27 cases presented fasting glucose of more than 7 mmol/L after nocturnal glucose of less than 3.0 mmol/L. Fasting glucose values below 3.9 mmol/l in the morning were associated with a 100% risk of nocturnal hypoglycemia, while fasting glucose values over 9.6 mmol/l in the morning were associated with no risk of nocturnal hypoglycemia. Correlation analysis showed that the nocturnal glucose nadir was significantly correlated with fasting glucose levels (r = 0.613, P < 0.001). Conclusions Our data provided no support for the existence of the Somogyi effect. If fasting glucose exceeds 9.6 mmol/L, we do not have to worry about asymptomatic nocturnal hypoglycemia in patients with type 2 diabetes.

Prevalence of nocturnal hypoglycemia in free-living conditions in adults with type 1 diabetes: What is the impact of daily physical activity?

ObjectiveStudies investigating strategies to limit the risk of nocturnal hypoglycemia associated with physical activity (PA) are scarce and have been conducted in standardized, controlled conditions in people with type 1 diabetes (T1D). This study sought to investigate the effect of daily PA level on nocturnal glucose management in free-living conditions while taking into consideration reported mitigation strategies to limit the risk of nocturnal hyoglycemia in people with T1D.MethodsData from 25 adults (10 males, 15 females, HbA1c: 7.6 ± 0.8%), 20-60 years old, living with T1D, were collected. One week of continuous glucose monitoring and PA (assessed using an accelerometer) were collected in free-living conditions. Nocturnal glucose values (midnight–6:00 am) following an active day “ACT” and a less active day “L-ACT” were analyzed to assess the time spent within the different glycemic target zones (<3.9 mmol/L; 3.9 – 10.0 mmol/L and >10.0 mmol/L) between conditions. Self-reported data about mitigation strategies applied to reduce the risk of nocturnal hypoglycemia was also analyzed.ResultsOnly 44% of participants reported applying a carbohydrate- or insulin-based strategy to limit the risk of nocturnal hypoglycemia on ACT day. Nocturnal hypoglycemia occurrences were comparable on ACT night versus on L-ACT night. Additional post-meal carbohydrate intake was higher on evenings following ACT (27.7 ± 15.6 g, ACT vs. 19.5 ± 11.0 g, L-ACT; P=0.045), but was frequently associated with an insulin bolus (70% of participants). Nocturnal hypoglycemia the night following ACT occurred mostly in people who administrated an additional insulin bolus before midnight (3 out of 5 participants with nocturnal hypoglycemia).ConclusionsAlthough people with T1D seem to be aware of the increased risk of nocturnal hypoglycemia associated with PA, the risk associated with additional insulin boluses may not be as clear. Most participants did not report using compensation strategies to reduce the risk of PA related late-onset hypoglycemia which may be because they did not consider habitual PA as something requiring treatment adjustments.

Twenty Years of Insulin Gla-100: A Systematic Evaluation of Its Efficacy and Safety in Type 2 Diabetes Mellitus.

IntroductionThis systematic review aims to present the current evidence base with respect to the initiation and intensification of insulin therapy with glargine 100 U/mL (Gla-100) compared to other insulins in people with type 2 diabetes mellitus (T2DM).MethodsA systematic literature search of PubMed (MEDLINE), EMBASE, and the Cochrane Central Register of controlled clinical trials databases was performed to identify studies published up to September 30, 2020 that compared the effects of Gla-100 to that of other insulin regimens in people with T2DM. Relevant information pertaining to the predefined outcomes of interest was extracted. Glycated hemoglobin (HbA1c) change and response rates along with overall hypoglycemia incidence were the primary efficacy and safety outcomes of interest.ResultsSeventy-nine studies (63 interventional and 16 non-interventional) in which Gla-100 was either initiated in previously insulin-naïve patients (n = 57) or used in an intensified regimen (n = 22) were identified and evaluated. In insulin-naïve patients, most studies demonstrated that Gla-100 was significantly better compared with premixed insulins and similar compared with neutral protamine Hagedorn (NPH) insulin, second-generation basal insulins, co-formulations, and other first-generation basal insulins in terms of the primary efficacy parameters. Overall hypoglycemia risk with Gla-100 was significantly lower compared with NPH, premixed, coformulation, and other first-generation basal insulins and significantly higher compared with second-generation basal insulins. In studies with intensified regimens, efficacy outcomes with Gla-100 were significantly better compared with insulin detemir (IDet); similar compared with NPH, second-generation basal insulins, co-formulations; and with premixed insulins. In these studies, overall hypoglycemia risk with Gla-100 was significantly lower compared with IDet and comparable to NPH, premixed insulins, co-formulations, and second-generation basal insulins. In addition, most intensification studies also revealed a significantly lower risk of nocturnal hypoglycemia with Gla-100–based regimens versus NPH and premixed insulins and a significantly greater risk compared to second-generation basal insulins.ConclusionsThe evidence presented in this review suggests that Gla-100 is an effective option for both insulin initiation and intensification strategies used in the management of T2DM.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-022-01284-2.

Continuous Glucose Monitoring-Recorded Hypoglycemia with Insulin Degludec or Insulin Glargine U100 in People with Type 1 Diabetes Prone to Nocturnal Severe Hypoglycemia.

Background and Aims: Nocturnal hypoglycemia is mainly a consequence of inappropriate basal insulin therapy in type 1 diabetes (T1D) and may compromise optimal glycemic control. Insulin degludec is associated with a lower risk of nocturnal hypoglycemia in T1D. As nocturnal hypoglycemia is often asymptomatic, we applied continuous glucose monitoring (CGM) to detect a more precise occurrence of nocturnal hypoglycemia in the HypoDeg trial, comparing insulin degludec with insulin glargine U100 in people with T1D and previous nocturnal severe hypoglycemia. Materials and Methods: In the HypoDeg trial, 149 people with T1D were included in an open-label randomized cross-over trial. Sixty-seven participants accepted optional participation in the predefined substudy of 4 × 6 days of blinded CGM requiring completion of at least one CGM period in each treatment arm. CGM data were reviewed for hypoglycemic events. Results: Treatment with insulin degludec resulted in a relative rate reduction (RRR) of 36% (95% confidence interval [CI]: 10%-54%; P < 0.05) in nocturnal CGM-recorded hypoglycemia (≤3.9 mmol/L), corresponding to an absolute rate reduction (ARR) of 0.85 events per person-week. In nocturnal CGM-recorded hypoglycemia (≤3.0 mmol/L), we found an RRR of 53% (95% CI: 36%-65%; P < 0.001), corresponding to an ARR of 0.75 events per person-week. At the lower detection limit of the CGM (≤2.2 mmol/L), treatment with insulin degludec resulted in a significant RRR of 58% (95% CI: 23%-77%; P = 0.005). The reductions were primarily due to significant RRRs in asymptomatic hypoglycemia. Conclusion: In people with T1D, prone to nocturnal severe hypoglycemia, insulin degludec compared with insulin glargine U100 significantly reduces nocturnal CGM-recorded hypoglycemia. www.clinicaltrials.gov (#NCT02192450).

Efficacy and safety of different basal and prandial insulin analogues for the treatment of type 2 diabetes: a network meta-analysis of randomized controlled trials.

The aim of the present network meta-analysis is to assess the efficacy and safety across different long and short-acting analogs for the treatment of type 2 diabetes. A PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases search (20th May, 2020) for all trials with a duration ≥24 weeks comparing an analogue with another or human insulin was performed. Indirect comparisons were performed by NMA choosing glargine U100 and human regular insulin, as the reference for long- and short-acting analogues, respectively. Primary endpoints were HbA1c at 24, 52, and 104 weeks. The weighted difference in means (WDM) and Mantel-Haenzel Odds Ratio [MH-OR] with 95% Confidence Intervals (CI) were calculated for categorical and continuous variables, respectively. Fifty trials (n = 43) and 7 for basal and prandial analogues, respectively, enrolling 25,554 and 3184 patients with type 2 and 1 diabetes, respectively, were included. At NMA, detemir was less effective than glargine U-100 at 52 weeks. A significant reduction of 24-week HbA1c (WMD [IC]: -0.10 [-0.17, -0.03]%); and risk of total (MH-OR [IC]: 0.80 [0.70, 0.91]), and nocturnal hypoglycemia (MH-OR [IC]: 0.57 [0.45, 0.73]) was observed for basal analogues versus NPH insulin. At NMA, glargine U300 and degludec were associated with a significant reduction in the risk of nocturnal hypoglycemia. No significant differences across different short-acting insulin were observed. This paper supports the use of long-acting analogues, rather than NPH insulin, as basal insulin for the treatment of type 2 diabetes, without any preferences for any individual long-acting analogue over the others. The evidence on short acting analogues is limited.

131-OR: ADA Presidents’ Select Abstract: Effect of Insulin Degludec vs. Insulin Glargine U100 on Occurrence of Nocturnal Hypoglycemia Assessed by Nocturnal Plasma Glucose Profiles in People with Type 1 Diabetes Prone to Nocturnal Severe Hypoglycemia

Background and Aims: The risk of nocturnal hypoglycemia (NH) is a limiting factor for achieving good glycemic control in people with type 1 diabetes (T1D). Insulin degludec (IDeg) is proven to lower the risk of self-reported NH. As most episodes of NH are asymptomatic, we assessed differences in occurrence of NH by hourly plasma glucose (PG) measurements at treatments with IDeg or insulin glargine U100 (IGlar) in people with T1D suffering from recurrent nocturnal severe hypoglycemia. Materials and Methods: Pre-defined optional substudy of the HypoDeg trial, a 2-year investigator-initiated, randomized, cross-over trial where 149 participants with T1D were randomized to treatment with IDeg or IGlar. Fifty-one participants (mean (SD) age 58 (13) years, diabetes duration 28 (14) years and HbA1c 7.8 (1) %) were admitted for two nights for hourly blinded plasma glucose measurements for a minimum of one night (23:00h to 07:00h) during each 1-year treatment period. The primary endpoints were NH at level 1 (PG ≤ 3.9 mmol/L) and level 2 (PG &amp;lt; 3.0 mmol/L). Results: We collected data from 196 nights. A total of 57 nights (regardless of level) in 33 participants were hypoglycemic, including 20 nights with symptomatic hypoglycemia. The incidence of NH at level 1 was lower when treated with IDeg [17 events in 97 nights (18%)] as compared to IGlar [36 events in 99 nights (36%)], corresponding to a hazard ratio (HR) of 0.39 (95% CI: 0.22-0.71; p=0.002) during treatment with IDeg. At level 2, the incidence of NH was also lower during treatment with IDeg [8 events in 97 nights (8%)] as compared to IGlar [20 events in 99 nights (20%)], corresponding to an HR of 0.36 [95% CI: 0.16-0.80; p=0.013] during treatment with IDeg. Conclusion: In people with T1D and recurrent nocturnal severe hypoglycemia, treatment with IDeg as compared to IGlar results in a clinically significant lower rate of NH at both levels of hypoglycemia. Disclosure J. M. Brøsen: None. S. Lerche: None. K. Nørgaard: Advisory Panel; Self; Medtronic, Other Relationship; Self; Novo Nordisk Inc., Zealand Pharma A/S, Speaker’s Bureau; Self; Medtronic. H. D. Parving: None. L. Tarnow: None. B. Thorsteinsson: None. U. Pedersen-bjergaard: Advisory Panel; Self; Novo Nordisk A/S, Sanofi-Aventis, Consultant; Self; Abbott, Speaker’s Bureau; Self; Novo Nordisk A/S. R. Agesen: Employee; Self; Novo Nordisk. P. L. Kristensen: Speaker’s Bureau; Self; AstraZeneca, Eli Lilly and Company. A. Alibegovic: Employee; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S. H. U. Andersen: Stock/Shareholder; Self; Novo Nordisk A/S. P. Gustenhoff: None. C. Hedetoft: None. T. Jensen: Stock/Shareholder; Self; Novo Nordisk A/S. C. B. Juhl: None. Funding Novo Nordisk

Use of Insulin Degludec/Insulin Aspart in the Management of Diabetes Mellitus: Expert Panel Recommendations on Appropriate Practice Patterns.

Insulin degludec/insulin aspart (IDegAsp) is a fixed-ratio co-formulation of insulin degludec (IDeg), which provides long-lasting basal insulin coverage, and insulin aspart (IAsp), which targets post-prandial glucose. This expert panel aimed to provide a practical and implementable guidance document to assist clinicians in prescribing IDegAsp in the diabetes management with respect to different patient populations including children and adults with type 1 diabetes (T1D) or type 2 diabetes (T2D) as well as pregnant, elderly and hospitalized patients and varying practice patterns (insulin-naive, insulin-treated, switching from basal, basal bolus and premix regimens). The experts recommended that IDegAsp can be used in insulin-naive T2D patients with poor glycemic control (HbA1c >8.5%) despite optimal oral antidiabetic drugs (OADs) as well as in insulin-treated T2D patients by switching from basal insulin, basal-bolus therapy or premixed insulins in relation to lower risk of nocturnal hypoglycemia, fewer injections and lower intraday glycemic variability, respectively. The experts considered the use of IDegAsp in children with T2D as a basal bolus alternative rather than as an alternative to basal insulin after metformin failure, use of IDegAsp in adult T1D patients as a simplified basal bolus regimen with lesser nocturnal hypoglycemia, fewer injections and better fasting plasma glucose control and in children with T1D as an alternative insulin regimen with fewer injection to increase treatment adherence. The proposed expert opinion provides practical information on use of IDegAsp in different patient populations and practice patterns to assist clinicians, which seems to compensate the need for easily implementable guidance on this novel insulin regimen.

Exenatide once weekly combined with metformin reduced glycemic variability in type 2 diabetes by using flash glucose monitoring system

BACKGROUNDMultiple studies demonstrate that fluctuating blood glucose level produces greater damage compared with sustained hyperglycemia. Flash glucose monitoring system is an effective method in documenting blood glucose variability, contributing to better glucose management and reduced hypoglycemic event occurrence.AIMTo investigate the improvement in glycemic variability (GV), blood glucose level, and metabolic indexes of patients with type 2 diabetes mellitus after combined treatment of exenatide once weekly (EXQW) and metformin.METHODSTwenty-five patients with type 2 diabetes mellitus suffering from poor blood glucose control under metformin treatment were recruited. The recruited patients were prescribed with oral metformin only (maintaining a dosage of metformin at ≥ 1500 mg/day) for 2 wk (screening period), and then given EXQW (2 mg, subcutaneous injection) for 12 wk (experimental period). The flash glucose monitoring system was used to document blood glucose values during the screening period and the last 2 wk of the experimental period. RESULTSFour patients were excluded for various reasons, yielding a total of 21 patients, including 17 males and 4 females, with an average age of 48.8 years, who completed this study. The estimated glycated hemoglobin, mean blood glucose, fasting and postprandial blood glucose levels, and percentage of blood glucose above 7.8 mmol/L decreased compared to those at baseline (P = 0.003, 0.003, 0.008, 0.010, 0.014, 0.017, and 0.005, respectively), while the percentage of blood glucose between 3.9 and 7.8 mmol/L significantly increased (P = 0.005). Parameters of GV including standard deviation of blood glucose, mean amplitude of glycemic excursions, mean of daily difference, area under the curve difference between percentiles 25 and 75, and area under the curve difference between percentiles 10 and 90 were significantly lower compared to that of baseline (P = 0.017, 0.006, 0.000, 0.024, 0.036, respectively). The durations of blood glucose below 3.9 mmol/L during the day and nocturnal periods significantly increased after treatment (P = 0.041 and 0.028, respectively), but there was no significant increase in severe hypoglycemia (< 3.0 mmol/L) compared with that at baseline (P = 0.207). In addition, some metabolic indicators improved after EXQW treatment.CONCLUSIONEXQW combined with metformin can effectively improve blood glucose levels, reduce GV, and improve metabolic indicators. However, there is still a risk of nocturnal hypoglycemia, and careful attention should be paid to patients with EXQW treatment.